1 P RIMARY CARE GUIDE TO A NTIDEPRESSANTS : P RESCRIBING , S TOPPING & S WAPPING Written – May 2019 Review – August 2020 Ratified at: Nottinghamshire Healthcare Trust TMOG, July 2019 Nottinghamshire Area Prescribing Committee, August 2019 Nick Sherwood, Mental Health Efficiencies Pharmacist
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PRIMARY CARE GUIDE TO
ANTIDEPRESSANTS:
PRESCRIBING, STOPPING & SWAPPING
Written – May 2019
Review – August 2020
Ratified at:
Nottinghamshire Healthcare Trust TMOG, July 2019
Nottinghamshire Area Prescribing Committee, August 2019
Nick Sherwood, Mental Health Efficiencies Pharmacist
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Nottinghamshire GP’s guide to antidepressants – Prescribing, swapping and stopping
May 2019 Nick Sherwood
In the role of interface pharmacist across Nottinghamshire Healthcare Trust and Nottinghamshire CCGs, I frequently take questions regarding practice with antidepressants from both primary and secondary care. Questions include how to monitor, when and how to switch and how to carry out reviews at regular check-ups. There is always confusion regarding which healthcare setting is responsible for this medication, and I found the guidance provided nationally to be overcomplicated or far too open to interpretation. The STAR*D trial addressed patient treatment strategies well. Most trials recruit through advertisement, use “pristine” patients with few co-morbidities, follow up the patients more frequently, and function without the possibility of counselling on medications due to blinding treatment, so algorithms guiding treatment are difficult to create. Choice of medication is often down to personal preference, adverse effects, personal circumstances and response to previous treatment. This being the case, this document will offer advice on the best approach to take when making changes to a depressed patient’s treatment. This document will remain within the confines of the Nottinghamshire Joint Formulary where possible. It will be kept up to date with any pertinent information that has resulted from queries relating to anti-depressant treatment across the interface. A full reference list can be found at the end of the document. Resources used include BAP, BNF, CKS, The Maudsley, Martindale: The Compete Drug Reference & NICE as well as a thorough literature review. NICE guidance on depression is due an update towards the end of 2019, and some of the suggestions to be made there will be explored in this document. Please don’t hesitate to contact me with questions regarding mental health medications, to discuss mental health medications across the interface, or future work you feel would be useful to strengthen prescribing across primary and secondary care. Nick Sherwood|Mental Health Efficiencies Pharmacist Greater Nottingham, Mid Nottingham CCGs/Nottinghamshire Healthcare NHS Foundation Trust [email protected] 07881010102
Contents 1. Treatment summary of current NICE Guidance (CG90) 2. Monitoring antidepressant treatment 3. Continuation of antidepressant treatment 4. Amending antidepressant treatment 5. Reducing doses and discontinuation 6. Serotonin syndrome 7. Useful Resources 8. FAQs Appendix 1: Sleep Hygiene Appendix 2: Info on medications Appendix 3: Switching Nottingham Formulary Antidepressants Appendix 4: Current Mental Health Efficiencies Project Documents Appendix 5: Nottinghamshire Formulary Traffic Light information
Treatment summary of current NICE Guidance (CG90) Diagnosis of depression is based on DSM-V criteria (CKS advice). First line treatment for recent onset/mild
depression is not medication, rather active monitoring, sleep hygiene, exercise, guided self-help and CBT.
Antidepressants are recommended for treatment of moderate or severe depression, subthreshold symptoms present for over 2 years, or mild depression that persists despite other interventions.
When discussing medication with the patient, discuss the choice and reasoning for it. Include side effects and potential discontinuation reactions (see monitoring treatment for more info on each).
Monitoring antidepressant treatment When initiating an antidepressant, a review period should be discussed with the patient. Try to arrange a review in 2-4 weeks for the first 3 months, and then if response to treatment is good longer intervals can be considered. During a review with a patient using antidepressants the following should be covered;
Check adherence to medication, any side effects
The risk of suicide
The person’s depressive symptoms (i.e. response to treatment?) – the PHQ-9 is a good resource
Any ongoing stresses that may contribute to depression
Assess the benefits of any psychological interventions
General information on side effects can be found in Appendix 2 If a patient suffers a side effect multiple strategies can be implemented. Symptoms can be monitored closely where they are acceptable (often the patient just needs reassurance, or the antidepressant can be stopped and switched to another if the patient prefers.
Continuation of antidepressant treatment The following are current NICE guidelines (CG90):
Support and encourage a person who has benefited from taking an antidepressant to continue medication for at least 6 months after remission of an episode of depression. (This greatly reduces the risk of relapse. Antidepressants are not associated with addiction).
Review with the person with depression the need to continue antidepressant treatment beyond 6 months after remission, taking into account - The number of previous episodes of depression - The presence of residual symptoms - concurrent physical health problems and psychosocial difficulties
When deciding whether to continue maintenance treatment beyond 2 years, re-evaluate with the person with depression taking into account age, comorbid conditions and other risk factors.
New NICE guidance (currently in draft, to publish late 2019) is set to strengthen these positions with the following;
For people who are continuing with medication to prevent relapse, maintain the same dose unless there is a good reason to reduce it (such as adverse effects)
For people continuing with medication to prevent relapse, hold reviews at 3, 6 and 12 months after maintenance treatment has started. At each review; monitor mood state using a formal validated rating scale, for example the PHQ-9, review side effects, review any personal, social and environmental factors that may impact on the risk of relapse, agree the timescale for further review (no more than 12 months). [new 2017]
Amending antidepressant treatment It is important to manage the expectations of the patient from the outset of treatment. Once a medication has been initiated, all antidepressants show a pattern of response where improvement is usually seen by the patient by
Check that the drug has been taken regularly and at the prescribed dose Those that show no discernible response at 3 weeks having taken the medication appropriately will probably never respond to that medication. Conversely those that show even small improvement at 3 weeks may go on to respond fully.
In individuals where no antidepressant effect is evident after 3-4 weeks, a change in dose or medication may be indicated.
NICE suggests evidence for switching from one antidepressant to another is more favourable than increasing the dose of an antidepressant. Generally switching with another SSRI before considering alternative class is the best course of action – many patients who cannot tolerate one SSRI will tolerate another. The choice of medication beyond the first SSRI should be individual and patient based. It should be informed by several factors that are unique to each patient:
Response to current medication/historical success
Secondary characteristics of the depression (i.e. insomnia, anxiety)
Side effects/issues the patient would wish to avoid (i.e. weight gain with mirtazapine)
Other medications (potential drug-drug interactions), or any contraindications/cautions for use. The time it takes to switch between antidepressants is informed by the half-life of medications (generally 5 half-lives until a medication reaches steady state or is excreted below therapeutic range), interactions between the medications, risk of serotonin syndrome and the reduction of potential discontinuation symptoms. Methods of swapping include cross tapering, taper to stop & start and abrupt switch. Switching antidepressants is covered in a table in Appendix 2.
Reducing doses & discontinuation symptoms Antidepressants taken for months should be withdrawn over weeks, and if taken for years withdrawn over months. Unless a serious adverse event has occurred, discontinuation symptoms can be avoided by proceeding slowly with caution.
NICE suggests a dose of antidepressants should be slowly reduced:
over 1 to 2 weeks if treatment has lasted less than 8 weeks over 6 to 8 weeks if treatment has lasted 6 to 8 months
Although antidepressants are not addictive they can cause serious discontinuation symptoms if stopped suddenly. Symptoms will usually occur within a few days of stopping treatment/reducing dose. The shorter the half-life of the medication the more likely discontinuation symptoms are likely to occur. These symptoms are varied, and can often present as similar to depressive symptoms (anxiety, insomnia).
Discontinuation symptoms are usually mild and will last between 1 and 2 weeks. Treatment of discontinuation symptoms is pragmatic. If symptoms are mild, it may be enough to simply reassure the patient that such symptoms are not uncommon and that they normally pass in a few days. If symptoms are severe, reintroduce the original antidepressants and taper more gradually. Remember by discontinuing/cross-tapering slowly and by educating the patient on what to expect, the symptoms (and a patient’s perception of their severity) will be lessened or avoided entirely. Antidepressants are not addictive!
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Mind have some useful counselling points on withdrawal of antidepressants for patients: https://www.mind.org.uk/information-support/drugs-and-treatments/antidepressants/withdrawal-effects-of-antidepressants
SSRI discontinuation (commonly associated with, but not limited to paroxetine): Commonly – Flu-like symptoms (chills, myalgia, excessive sweating, headache, nausea, goose-bumps), ‘shock-like’ symptoms, dizziness exacerbated by movement, insomnia, excessive dreaming, irritability, crying spells, nausea, vomiting, diarrhoea Less commonly – Movement disorders, problems with concentration and memory
TCA discontinuation (commonly associated with , but not limited to amitriptyline and imipramine): Commonly – Anxiety, flu like symptoms (chills, myalgia, excessive sweating, headache, nausea, goose-bumps), insomnia, excessive dreaming, restlessness Less commonly - fast/irregular heartbeat, movement disorders, mania
MAOI discontinuation (all carry a high risk) Commonly – Agitation, irritability, difficulty thinking, ataxia, movement disorders, insomnia, somnolence, vivid dreams, cognitive impairment, slowed speech, Less commonly – Hallucinations, paranoid delusions
SNRI discontinuation (venlafaxine, duloxetine) Commonly – Dizziness, sensory disturbances, sleep disturbances, agitation or anxiety, nausea and vomiting, tremor, vertigo, headache, flu symptoms. Less commonly - symptoms may be more severe or prolonged
Mirtazapine discontinuation (may happen after long term use, majority mild and self-limiting) Commonly – dizziness, orthostatic hypotension , headache, increased appetite Less commonly – lethargy, nausea, agitation, anxiety
Serotonin Syndrome Serotonin syndrome can occur with the use of high dose serotonergic agents – usually after the introduction of a second to a patient. It is caused by excessive central and peripheral serotonergic activity. Onset of symptoms can occur within hours or days of increase in serotonergic medication. Causative agents should be stopped, and decisions leading up to the choice of medication re-assessed. It is classed as poisoning, and severe symptoms will need urgent management in an acute care setting. Symptoms generally have 3 forms, outlined well by UKMi;
UKMi have a very good summary of serotonin syndrome: https://www.sps.nhs.uk/articles/what-is-serotonin-syndrome-and-which-medicines-cause-it-2/
Useful resources For information on mental health medications, take a look at: https://www.choiceandmedication.org/nottinghamshirehealthcare/ Mind have useful patient-facing information: https://www.mind.org.uk/information-support/drugs-and-treatments/antidepressants/about-antidepressants/#.XFqs_KBpTMA Nottinghamshire Healthcare Trust have access to Recap, which allows the sharing of useful information for patients. Email [email protected] for details. Trazodone, Trimipramine and Dosulepin deprescribing documents can be found here: https://www.nottinghamshiremedicinesmanagement.nhs.uk/policies-and-documents/mental-health-efficiencies/ MHRA ALERTS https://www.gov.uk/drug-safety-update/citalopram-and-escitalopram-qt-interval-prolongation
FAQs This section will be updated with further useful information as a result of developments, or queries related to antidepressants.
September 2019 – Dispersible fluoxetine
Currently fluoxetine 10mg capsules and tablets are very expensive, so their use is not recommended. There are two alternative preparations – dispersible fluoxetine (Olena®) and liquid. Of these two, fluoxetine 20mg/5ml oral solution (70ml) is the most cost effective option and so is preferable in patients using 10mg OD.
References Literature review carried out 7/11/2018 on PubMed, EMBASE and Medline using the terms “depression” & “primary care”. NICE depression in adults: treatment and management (In development [GID-CGWAVE0725], expected publication date: 13 December 2019) (link), last accessed 18/12/2018 NICE Clinical Guideline (CG90) – Depression in adults: recognition and management (2009), link
NHS common health questions – “How should antidepressants be discontinued?” - link Clinical Knowledge Summaries (CKS), Depression (link), last accessed 19/12/2018 Patient Health Questionnaire – PHQ-9, available from http://www.psycho-oncology.info/PHQ9_depression.pdf, last accessed 19/12/2018 Taylor, D. Barnes, T. Young, A. The Maudsley Prescribing Guidelines 13th Edition. Wiley Blackwell, 2018 He H et al. Efficacy and tolerability Efficacy and tolerability of different doses of three new antidepressants for treating major depressive disorder: A PRISMA-compliant meta-analysis. J Psychiatry Res 2018;96:247-259 Gaynes et al (2008), The STAR*D study: Treating depression in the real world. Cleveland Clinic Journal of Medicine, Vol75, No1 UKMi Q&A – What is serotonin syndrome and what causes it? – link NPS MedicineWise - Oral and dental effects of antidepressants - https://www.nps.org.au/australian-prescriber/articles/oral-and-dental-effects-of-antidepressants Glue, P. Donovan, MR. Kolluri,S. Emir, B. (2010), Meta-analysis of relapse prevention antidepressant trials in depressive orders, Aust NZ J Psychiatry, 2010 Aug;44(8):697-705
Please don’t hesitate to contact me with any questions/suggestions. Nick Sherwood|Mental Health Efficiencies Pharmacist
Appendix 1: Sleep Hygiene A good booklet on “Managing Insomnia and Sleep Problems” is available here. The booklet includes “10 Rules for Improved Sleep Hygiene”;
1 Discontinue caffeine use 4 hours before bed time
2 Avoid smoking around bed time, and when you wake up during the night
3 Avoid alcohol around bed time. Although it may get you to sleep, it can disrupt sleep later on in the night
4 A light snack at bedtime may promote sleep, but avoid large meals
5 Try to do mild exercise regularly, but avoid vigorous exercise within 2 hours of bed time
6 Keep your bedroom calm and comfortable
7 Keep your bedroom a comfortable temperature
8 Minimise noise and light in the bedroom, but spend time in sunlight during the day
9 Keep your bedroom mainly for sleeping; avoid watching television, using your phone, eating in the bedroom
Cognitive Behavioural Therapy (“Talking Therapy”) in Nottinghamshire Treating issues around sleep is a process that cannot be addressed by the use of medications alone. There are several “talking therapy” services across Nottinghamshire that patients can refer themselves to, or with consent healthcare providers can refer them to.
Vortioxetine Taper and stop, then start at low dose
Taper and stop, then start fluoxetine at 10mg/day (liquid)
Cross taper cautiously
Taper and stop, wait for one week THEN start moclobemide
Taper and stop, wait for ONE week THEN start phenelzine
Cross taper cautiously, start SNRI at low dose.
Cross taper cautiously, start at low dose.
Cross taper cautiously, start low dose trazodone
Cross taper cautiously, start at low dose.
*Amitriptyline is GREY for depression
“Cross taper cautiously” This refers to a technique where over the course of several weeks (several months if the patient is established on the current
medication), a slow reduction of the dose through 4 dosing steps. For example where sertraline may have been used at 100mg, reduce to 75mg on step 1,
50mg on step 2, 25mg on step 3 then stop on step 4. The alternative medication should be started during this period. Be cautious of interaction or
synergistic side effects between the two medications.
“Cross taper cautiously, start with a low dose” Usually this means the new dose should be started more cautiously. For example, venlafaxine being
introduced at a low dose would be introduced at 37.5mg (the lowest dose available).
“Abrupt switch” In some rare cases an abrupt switch may be made.
“Taper and stop, then start with a low dose” Measured reduction of the medication through 4 dosing steps should be made. Only when the medication has
stopped should the new one start. This is usually due to a longer half-life of one of the medications making clearance a slower process.
“Taper and stop, wait x weeks, the start” Again due to a longer half-life of the medications, resulting in a gap between treatments being required in order
to safely proceed. You will see this approach for switches incorporating MAOis, it is a tactic to avoid serotonin syndrome among other issues.
Switching within class
When it comes to switching between the same class (SSRI/SSRI, TCA/TCA), the advice is usually cross taper cautiously, starting at a low dose. The speed of
cross-tapering is judged by monitoring patient tolerability. In some cases the pharmacodynamics of a certain medications may allow an immediate switch
(i.e. fluoxetine has a long half-life which makes this possible). It is important to remember the potential dangers of simultaneously administering two
antidepressants. They could work synergistically to lead to pharmacodynamics issues (Serotonin syndrome, hypotension, drowsiness).
If you have read this document and still require further guidance, please contact either the author;